Yellow fever Vaccine investment strategy

Yellow fever Vaccine investment strategy Background document #5 November 2013

Executive summary Since 2001, GAVI has spent ~$250M on yellow fever control $102M on routine vaccination in 17 countries ~$160M on campaigns in "A" risk countries 1 and epidemic response (through the stockpile) Additional GAVI support for yellow fever campaigns could help prevent future epidemics at a relatively low cost compared to other vaccine investments Investment scenario: contingent on completion of risk assessments, one-time campaigns in unvaccinated populations in countries previously targeted with mass campaigns as well as GAVI eligible "B" risk countries 1 High value for money, with a cost of ~$1600 per death averted Promotes supply stability and could potentially lower price Low risk of operational challenges given existing experience supporting yellow fever mass campaigns; possible challenges in planning and execution of risk assessments Potential downsides of the investment Low overall direct health impact relative to most current GAVI vaccines, explained by small country scope (~10 out of 56 GAVI-eligible countries based on current risk assessment) and epidemic nature of disease Uncertainty of exact campaign need and cost implications linked to dynamic nature of YF epidemiology Recommendation: support new yellow fever vaccine campaigns and develop a process for the funding of individual campaigns on the basis of robust risk assessments. Projected costs: ~$140 over 2015-2030 1. WHO defines "A" risk countries as countries reporting multiple YF outbreaks ( 2) in the previous 30 years; "B" risk countries are countries reporting at least one YF event in the previous 50 years and with evidence of YF circulation 1

Key yellow fever vaccine benefits Key benefits Health impact Epidemic potential Impact on vaccine markets Cost Value for money (relative to current portfolio) Unique global and country implementation requirements Country views Potential to avert disruptive epidemics Opportunity to shape / stabilise vaccine market Low implementation risk, proof of concept Yellow fever can suddenly re-emerge after decades, affecting all ages and leading to fear in communities; vaccine likely to offer lifetime protection to those immunised Forecasted campaign demand is 78M doses through 2021: will promote supply stability and could drive price decline Successful mass campaigns already implemented in 12 countries; GAVI has experience supporting 1. Does not include emergency stockpile 2

No major challenges foreseen with YF campaigns Key challenges Health impact Epidemic potential Uncertainty about need for additional campaigns Some uncertainty about future need for campaigns due to changing YF epidemiology and country risk profiles Impact on vaccine markets Cost Value for money Unique global and country implementation requirements Country views Requires robust process for planning, funding and monitoring campaigns Priority in small subset of GAVI countries only Process for planning, funding and monitoring campaigns could be strengthened; robust risk assessments of critical importance for effective implementation Country scope includes 10 of 56 GAVIeligible countries 3

Yellow fever vaccine investment scenario: add mass campaigns in high risk countries Strategies and assumptions are for modeling purposes. Actual implementation strategies will be based upon latest guidance received from WHO s Strategic Advisory Group of Experts and other WHO expert bodies. All strategies are modelled without financial constraints Doses Target population Base case: high risk populations in "B" risk endemic countries and remaining unvaccinated population in one "A" risk country (>9 months) 1 Single dose High need: unvaccinated population in all "A" risk countries + additional high risk populations in "B" risk countries (>9 months) 1 1. WHO defines "A" risk countries as countries reporting multiple YF outbreaks ( 2) in the previous 50 years; "B" risk countries are countries reporting at least one YF event in the previous 50 years and with evidence of YF circulation 4

Base case need estimated to be 78M doses; high need could add ~137M doses (through 2030) Doses (M) 20 Base scenario High scenario 15 10 5 0 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 # countries starting campaigns 2 0 1 0 3 1 3 TBD TBD TBD TBD TBD TBD TBD TBD TBD 5

Base case: potential to avert 104,000 deaths at a total cost of $163 M over 2015-2021 period Base case: mass campaigns in A and B risk countries (2015-2021) Base case + high need: additional campaigns in A and B risk countries (2022-2030) Fully vaccinated persons 70 M 194 M Impact Total future deaths averted 104,000 Not modeled Deaths averted per 100k vaccinated 147 Not modeled GAVI procurement cost $94 M $258 M GAVI operational costs $46 M $128 M Cost Total GAVI cost $140M $386M Country operational costs $22 M $62 M Total cost $163 M $448 M Value for money Total cost per death averted $1,600 Not modeled 6

Yellow fever campaigns would have moderate direct impact and reduce risk of epidemics Future deaths averted per 100k vaccinated 1 1,000 5,000 1,500 Disruptive epidemic potential (deaths averted less relevant metric) 800 768 668 600 576 541 400 200 198 147 0 Rabies HPV Hep B Pneumo Hib Malaria Rota Yellow2 Fever 63 45 31 29 24 Rubella Influenza Cholera Men A JE 1. Over 2015-2030 2. VIS only Note: Model outputs shown for base case (10 campaigns) Source: Imperial College Impact model 7

Low impact relative to other investments due to small scope (~10 campaigns) Future deaths averted, 2015 2030 (M) 8 6.6 Disruptive epidemic potential (deaths averted less relevant metric) 6 4.9 4.3 4 2.7 2 1.2 1.1 Countries introduced with GAVI support 0 66 66 63 48 50 34 34 45 45 10 21 26 6 1. VIS only Note: Model outputs shown for base case (10 campaigns) Source: Imperial College impact model 0.3 0.2 0.2 0.10 0.08 0.06 0.02 Hep B Hib Pneumo HPV Rota Malaria Rubella Influenza Rabies Yellow Cholera Men A JE 1 Fever Note: green indicates vaccine would only be rolled out in a subset of GAVI countries 8

Additional yellow fever campaigns constitute a relatively small investment Total cost to GAVI, 2015 2030 ($B) 1 10 8 Disruptive epidemic potential (deaths averted less relevant metric) 8.1 6 4.5 Countries introduced with GAVI support 4 2 0 0.09 0.12 0.14 0.3 JE Rabies Yellow Fever 2 0.6 0.7 1.2 2.0 2.6 3.1 Men A Rubella Influenza Cholera HPV Malaria Rota Penta Pneumo 6 45 10 26 34 45 21 48 34 50 66 63 Note: green indicates vaccine would only be rolled out in a subset of GAVI countries 1. Includes GAVI procurement cost + vaccine introduction grants + GAVI operational cost grants; 2. VIS only Note: model output based on base case (~10 campaigns); Source: GAVI Financial Forecast v7.0fb as of July 2013, VIS analysis 9

Yellow fever campaign investment is relatively strong value for money Total cost 1 per death averted, 2015 2030 ($'000) 55 Disruptive epidemic potential (deaths averted less relevant metric) 17.4 15 12.0 10 6.1 5 0.7 0.8 1.2 1.6 2.6 2.6 3.1 3.5 5.0 0 Penta 2 Rabies HPV Yellow3 Fever Pneumo Rubella Malaria Rota Influenza JE Men A Cholera 1. Includes operational + procurement cost to GAVI and country 2. Includes deaths averted for Hep B and Hib 3. VIS only Note: Model outputs base case (~1 campaigns) Source: GAVI Financial Forecast v7.0fb as of July 2013, VIS analysis 10

¼ of respondents rated yellow fever campaigns as a priority Survey: yellow fever a lower priority in overall sample of respondents % of respondents ranking disease as 1 or 2 100 Quotes from in-depth country interviews Yellow fever mass campaigns are game changers. 80 60 40 20 75 40 40 24 21 "We tend to under estimate the impact of YF. Once you see an epidemic, you pray not to see another one in your life time! Campaigns are feasible, but they are challenging Malaria Cholera Rabies Yellow Fever Influenza Average priority 1.9 2.8 3.1 3.8 3.4 Source: 2013 GAVI country consultation survey, total responses = 182, 57 from countries in scope for yellow fever campaigns (VIS) Question: Please rank all of the following vaccines in terms of prioritisation for future introduction in your country 11

Majority of respondents see campaigns as feasible and desirable within 3-5 years How feasible do you think the proposed campaign would be in your country? When would you want to introduce yellow fever vaccines in your country? # of responses 15 15 # of responses 25 23 12 20 17 10 10 15 10 9 5 6 5 1 2 0 Easily feasible Feasible with small additional investments Feasible with significant additional investments Not feasible 0 Within the next 3 years In the next 3-5 years In the next 6-10 years Will probably not introduce No opinion Source: 2013 GAVI Phase II country consultation survey, total n = 182; yellow fever-specific questions asked only to respondents ranking yellow fever as a first of second priority for introduction 12

Country level Global level No special, challenging implementation requirements foreseen Area of focus Unique implementation requirements Unique costs Policies and processes Requires robust process for planning, funding and monitoring campaigns; stockpile management requirement WHO stockpile management costs Supply Limited production capacity, due to be expanded in 2016; need to ensure current efforts to overcome these difficulties are successful No direct costs Health workforce No unique health workforce requirements for implementing campaigns N/A Social mobilisation, education, communication Yellow fever is well known in endemic countries so there is no special need for intensified IEC N/A Supply chain infrastructure and logistics May require significant cold-chain capacity due to large target population No direct costs Surveillance Risk assessments must be conducted before mass campaigns Need to maintain and strengthen surveillance system (integrate remaining at-risk countries, enhance lab capacity and quality, improve sample collection and transportation) Risk assessments (business plan) Planning, coordination, integration N/A N/A Unique but manageable May not be manageable in short term / within current GAVI model 13

Options for a yellow fever investment Support new yellow fever vaccine campaigns and develop a process for the funding of individual campaigns on the basis of robust risk assessments Allocate funding (capped) for new campaigns in specific countries / target populations currently identified by WHO at a total cost to GAVI of $140 M Allocate funding (capped) for new campaigns in specific countries / target populations, high need scenario (with additional campaigns on top of current WHO request) at a total cost to GAVI of $386 M Do not to support new yellow fever campaigns Recommended option 14

Implications of no GAVI support 1. Risk of YF resurgence and urban outbreaks if preventive campaigns are not conducted in targeted countries, necessitating urgent response 2. Unfunded demand for yellow fever vaccine could lead to higher prices and less reliable supply 15

Yellow fever: experts and sources consulted Sources WHO Addendum to Strategic Framework for Yellow Fever Immunization Initiative in Africa 2012-2020 (July 2013) WHO Yellow Fever Initiative Joint WHO and UNICEF progress reports, Annexes (2009, 2010, 2011) Garske T, Kerkhove M, Yactoyo S, Ronveaux O, Lewis R, Staples J, Perea W, Ferguson N, et al. (2012) Yellow Fever in Africa: burden of disease and impact of mass vaccination. Yellow Fever, WHO Position Paper, July 2013 Experts Sergio Yactayo, WHO Alejandro Costa, WHO William Perea, WHO Oyewale Tomori, Redeemer's University, Nigeria Rosamund Lewis, Public Health Agency of Canada (former WHO, former GAVI) Erin Staples, CDC Michel Van Herp, MSF Michael Clark, GAVI consultant (MC Consulting) 16

Appendix 17

Demand forecasting assumptions Base case per WHO recommendation: one "A" risk and nine "B" risk gavieligible countries Element Assumptions Rationale / source Country scope Target population Introduction dates Uptake Analogue Coverage Products Logistics "A" risk country (1), "B" risk countries (9), per current WHO recommendation High risk populations as defined by WHO risk assessment Campaigns span multiple years from 2015-2021 Instant uptake Demand: 100% of high risk target population FVP: MSIA coverage Products from 4 manufacturers (WHO pre-qualified); lyophilised, 5-, 10-, and 20- dose vials Wastage Factor: 1.11 (10% wastage rate) Expansion of current support to "A" and "B" risk countries as defined in WHO YF Strategic Framework High risk populations are targeted to decrease potential for epidemic outbreak WHO input Standard GAVI analogue for campaigns WHO input and standard SDF assumption Manufacturer product insert WHO recommendation for 10 dose lyo product 18

High need scenario forecasting assumptions Additional mass campaigns in "A" and "B" risk countries Element Assumptions Rationale / source Add. demand Add. total cost Country scope and target population "A" risk countries all remaining unvaccinated individuals "B" risk countries in endemic areas without routine YF coverage + additional countries suggested by experts 80% of unvaccinated individuals Potential need to vaccinate all unvaccinated individuals given the high risk of YF in these countries Countries without YF routine vaccination have a moderate risk of having a outbreak; additional high risk countries suggested by experts 11 M $24M 126 M $262M Total 144 M $285M Note: Other assumptions remain the same as in base case: instant uptake, FVP MSIA coverage, products from 4 manufactures and wastage factor of 1.11 19

Yellow fever vaccine impact modelling assumptions Imperial College 1 Model structure Generalized linear model Markov Chain Monte Carlo techniques used to combine several inputs: Environmental data, serological surveys, disease occurrence, surveillance quality, demographic data, age dependent vaccination coverage, etc. Produces estimates of yellow fever deaths and cases averted Counterfactual is coverage without additional campaigns Key assumptions Vaccine efficacy: 100% (WHO) Disease severity: 10% of infections presented as severe cases Severity leading to death: 20% of severe cases of yellow fever eventually lead to death Surveillance quality: 29,237 records of suspected cases of yellow fever used from 21 countries (YFSD) Disease occurrence: database of reported outbreaks in the 25 year period between 1987 and 2011 is used Age dependent vaccination coverage: 2011 EPI coverage rates used 1 Garske T, Kerkhove M, Yactoyo S, Ronveaux O, Lewis R, Staples J, Perea W, Ferguson N, et al. (2012) Yellow Fever in Africa: burden of disease and impact of mass vaccination. 20

Yellow fever transmission in Africa Source: CDC - http://www.cdc.gov/yellowfever/maps/africa.html 21

GAVI has supported yellow fever efforts in 20 countries to date Country Routine intro year Campaign year Benin 2002 2009 Burkina Faso - 2008 Cameroon 2004 2009 CAR 2000 2010 CHAD 1985 - DRC Congo 2004 - Congo Republic 2004 - Cote d'ivoire - 2011-2012 Ghana 1992 2011-2012 Guinea 2002 2010 Guinea Bissau 2008? - Kenya 1992 - Liberia 2001 2009 Mali 1992 2008 Niger 2000 - Nigeria 1992 - Sao Tome Principe 2003 - Senegal - 2007 Sierra Leone 2002 2009 Togo 1992 2007 Source: GAVI yellow fever reporting 22

GAVI has spent $253M on yellow fever since 2001 $M 60 60 40 38 30 31 20 16 19 17 17 0 2 2 10 7 6 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 Routine (procurement) Campaign (procurement) Campaign (operational) Stockpile (procurement) Stockpile (operational) 1 1. Operational cost under investment case UNICEF Source: GAVI YF Investment 2002-2013 overview 23

WHO designates countries by their risk of having a yellow fever outbreak "A" Countries "B" Countries "C" Countries Countries reporting multiple YF outbreaks ( 2) in the previous 30 years Benin Burkina Faso Cameroon Central African Republic Cote d'ivoire **Ghana Guinea Liberia Mali Nigeria Senegal Sierra Leone Togo Countries reporting at least one YF event in the previous 50 years **Angola Chad **Congo DR Congo Ethiopia Guinea Bissau Kenya Mauritania Niger South Sudan Sudan Uganda No reported outbreaks within last 50 years; low current risk Burundi **Equatorial Guinea Eritrea **Gabon Gambia Rwanda Sao Tome Principe Somalia Tanzania **Countries projected to be non-eligible as of eligibility policy 2013 24